title: Bone marrow suppression or active proliferation? An analysis of neutropenia after pegylated interferon treatment of patients with chronic hepatitis C.
abstract: BACKGROUND
  Neutropenia is a common adverse effect of the treatment of chronic hepatitis C with pegylated interferon and ribavirin. However, the mechanism involved is unknown. The present study aimed to investigate the cause of treatment-induced neutropenia by determining cytokine levels in plasma and in bone marrow smears.
  
  
  METHODS
  Fifteen patients with chronic hepatitis C were enrolled in this study. Plasma cytokine levels were determined using the Luminex assay before and during treatment. We simultaneously determined the levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and 7 other cytokines, and performed bone marrow cytology when blood cell counts indicated neutropenia.
  
  
  RESULTS
  Only 1 bone marrow smear indicated a low cell proliferation level, whereas active proliferation was observed in the remaining 14 patients. The levels of G-CSF, GM-CSF, interleukin (IL)-2, IL-4, IL-6, and interferon (IFN)-γ decreased significantly in patients with neutropenia (p < 0.05). In contrast, the levels of IL-8, IL-10, and tumor necrosis factor (TNF)-α showed no significant change (p = 0.713, 0.930, 0.833, respectively) before or after treatment.
  
  
  CONCLUSIONS
  The bone marrow of most patients with IFN-induced neutropenia showed active cell proliferation. Elevated G-CSF and GM-CSF but not bone marrow suppression was observed along with neutropenia after pegylated interferon treatment, suggesting a causative role of G-CSF and GM-CSF in neutropenia.
authors.affiliation: From the Hepatology Department, Youan Hospital, Capital Medical University , Beijing , China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Liu
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Du
authors.forename: Xin-Yue
authors.initials: XY
authors.lastname: Chen
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Ma
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Guo
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Lu
authors.forename: Zhen-Huan
authors.initials: ZH
authors.lastname: Cao
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology; D016207:Cytokines / Q000097:blood; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced* / Q000473:pathology*; D011092:Polyethylene Glycols / Q000009:adverse effects* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a